Two drugs are better than one for asthma control: study

NEW YORK (Reuters Health) - People with asthma are likely to
benefit from combining medications to manage their symptoms, a
strategy that requires doctors and patients to work together to
tweak prescriptions, Dutch researchers say.

Based on a review of data from 64 asthma drug trials, the
new study found that patients using inhaled corticosteroids with
a long-acting bronchodilator had about half as many symptom
flare ups and asthma attacks as those just on the steroids.

"There were some things we expected beforehand, like that
oral therapies would be inferior to inhaled steroids, but asthma
is a very individual disease and some patients will not
experience any symptoms and other patients will suffer a lot
from the symptoms," said lead author Dr. Rik Loijmans, from the
Academic Medical Center at the University of Amsterdam.

Although the worst breathing problems associated with asthma
usually occur in episodes or "attacks," the problem of a
sensitive, swelling airway is constant. Treating asthma means
being able to take medication that works quickly to relieve an
attack as well as one that will keep the swelling under control,
he told Reuters Health.

Worldwide, approximately 300 million people have been
diagnosed with asthma, according to the Global Initiative on
Asthma (GINA). That number is expected to rise to 400 million by
2025.

Asthma rates in North America are among the highest in the
world, according to GINA, with some 36 million cases in the U.S.
and Canada, representing more than 11 percent of the total
population.

While corticosteroids can keep airways from swelling and
building up with mucus, long-acting beta antagonists (LABAs)
keep the muscles of the airways relaxed, resulting in fewer
asthma attacks.

Normally, when patients are diagnosed with asthma, they are
first treated with low-dose inhaled corticosteroids, and if
there is reason to step up the therapy, such as recurring
attacks, then the dose would likely be raised. Adding more drugs
to the treatment regimen would come later.

Some products combine steroids with LABAS in a single
treatment, such as GlaxoSmithKine's Advair and AstraZeneca's
Symbicort. But in the U.S., those products carry a "black box"
warning, which discourages their being used widely, researchers
said.

To compare the effectiveness of all available asthma
management strategies, Loijmans and his colleagues sifted
through data from drug trials and selected the ones that met
their criteria for making the results comparable. For instance,
trials had to last 24 weeks or more, all patients had to have
moderate to severe asthma, to have used a "rescue drug" to stave
off an attack, or to have experienced nighttime waking because
of an asthma episode.

"It scares me a bit to think that that there is such an
ailment that so many people suffer from and receive years of
treatment for yet there are only 64 trials with duration of more
than 24 weeks published," Loijmans said.

The researchers compared 15 different drug management
combinations to one another, and to treatment just with a low
dose of the anti-inflammatory corticosteroids.

The trials included drugs that prevent swelling, as well as
drugs that block immune system chemicals that can trigger
attacks and those classified as rescue or "reliever" drugs, to
be used specifically in the case of an asthma attack. The study
team gauged the safety of medications by counting how many
people dropped out of a trial

"A side effect in the trial that results in dropping out
means that that person would have had a bad reaction to the
medication if they had tried it outside of a study and that
means it wasn't very effective in helping that patient,"
Loijmans said.

Overall, the combination of inhaled corticosteroids with
LABAs - either as two separate drugs, or in a fixed dose
delivered together - were the most effective at reducing the
number of attacks patients experienced, according to the results
published in the British medical journal BMJ.

Combinations of other drug types were not better than
corticosteroids alone, and no single drug was better than
steroids alone either.

The combination regimen also proved safe, according to the
study results, including the products that combine two drugs
into one treatment.

"Yet, these are the products with black box warnings," noted
Dr. Ken Chapman, director of the Asthma and Airway Centre of the
University Health Network in Ontario, Canada.

The U.S. Food and Drug Administration (FDA) required the
black box label because the combination products were associated
with an increased risk of wheezing, which can lead to an asthma
attack, according to Chapman.

That makes patients leery of the products and doctors
hesitant to prescribe them, he said.

Chapman told Reuters Health that the Dutch researchers'
analysis and conclusions are not surprising, in fact, they are
very well known, but the review is the most rigorous
presentation of the data he has ever seen.

"It's interesting that the FDA is willing to ignore this
knowledge but there is a reason the drugs are still on the
market. The world knows that this combination is effective,"
Chapman said.